Normal human somatic cells have finite replicative life-spans when cultured in vitro. This phenomenon of "clonal senescence" may be regarded as a useful model for the study of certain aspects of cell aging. The proposed experiments attempt to elucidate the mechanism(s) of such clonal senescence by a variety of somatic cell genetic experiments involving heterokaryons, synkaryons and hybrids between post-replicative "old" cells and both normal diploid and heteroploid actively replicating cells. In one line of experiments, temperature sensitive cell cycle mutants will be employed in attempts to identify a specific protein which can re-initiate DNA synthesis in "senescent" post-replicative cells. The general hypothesis being tested is that clonal senescence is initiated by a process analogous to cell differentiation. BIBLIOGRAPHIC REFERENCES: Martin, G. M., Norwood, T. H., and Hoehn, H. Somatic cell genetic investigations of clonal senescence. In: International Symp. Molecular Biology of the Mammalian Genetic Apparatus--Its Relationship to Cancer, Aging and Medical Genetics (Ed. Paul O.P. Ts'o), Elsevier-Excerpta Medica Press, North-Holland, in press (1976). Norwood, T. H., Hoehn, H., Martinez, A. O. and Martin, G. M. Synkaryon and heterokaryon analysis of clonal senescence. Proceedings from meeting entitled: "Is Senescence Dominant or Recessive in Somatic Cell Crosses?" Camden, New Jersey, May 14, 1976. Plenum Press, in press 1976.